scholarly journals The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps

2020 ◽  
Vol 176 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Vicki L Sutherland ◽  
Charlene A McQueen ◽  
Donna Mendrick ◽  
Donna Gulezian ◽  
Carl Cerniglia ◽  
...  

Abstract There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, “The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity” (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.

2017 ◽  
Vol 1 ◽  
pp. 239784731774188 ◽  
Author(s):  
Elena Scotti ◽  
Stéphanie Boué ◽  
Giuseppe Lo Sasso ◽  
Filippo Zanetti ◽  
Vincenzo Belcastro ◽  
...  

The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.


2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.


2019 ◽  
Vol 8 (5) ◽  
pp. 693 ◽  
Author(s):  
Yunju Jeong ◽  
Ji-Won Kim ◽  
Hyun Ju You ◽  
Sang-Jun Park ◽  
Jennifer Lee ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1547-1547
Author(s):  
Sarah Berry ◽  
Jose Ordovas ◽  
Francesco Asnicar ◽  
Ana Valdes ◽  
Paul Franks ◽  
...  

Abstract Objectives The human gut microbiome plays a critical role in host glucose metabolism, but its connections to other key markers of cardiometabolic health in fasting and postprandial conditions is largely unknown. The PREDICT 1 study enrolled n = 1,102 twins and unrelated healthy US/UK adults to explore the genetic, metabolic, microbial, and meal determinants of fasting metabolites and postprandial responses to foods. Methods This multi-centre dietary study assessed fasting and postprandial (0-6h) circulating metabolites over a 13d study period incorporating standardized test meals of varying nutrient composition. Shotgun metagenomics was performed from samples collected at baseline (n = 1,001 UK and 97 US). Metabolomics (NMR) was performed on clinic fasting and postprandial samples, blood glucose was continuously assessed, and blood triglycerides and C-peptide were serially measured. Results Using machine learning models, we found the fasting metabolites most strongly associated with overall gut community structure were the inflammatory marker GlycA (r = 0.31), and HDL and VLDL particle diameter (HDL-D and VLDL-D; r = 0.3 and 0.28 respectively). Variance explained was slightly greater for postprandial HDL-D and VLDL-D (at 6h; r = 0.32 and 0.31, respectively) than fasting levels, whilst the other metabolites did not differ (e.g., GlycA r = 0.28). Lipid-mediated metabolites were more closely associated with the gut microbiome in both fasting and postprandial states compared with glycemic-mediated measurements. There were distinct microbial clusters that segregated both fasting and postprandial metabolites according to their known association with cardiometabolic disease; ApoA and HDL vs. ApoB, VLDL, IDL LDL, remnant C, GlycA, IL-6, blood pressure, glucose, insulin and HbA1c. We also identified differential abundance among several microbes associated with metabolic health, including Prevotella copri and Faecalibacterium prausnitzii. Results obtained in the UK cohort were validated in the US cohort. Conclusions An individual's gut microbial composition is predictive of their cardiometabolic markers and personalized responses to food. Our data highlight the potential of the gut microbiome as a target amenable to modulation in personalized nutrition to ameliorate cardiometabolic risk. Funding Sources Zoe Global Ltd., NIHR GSTT BRC, Wellcome Trust.


Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 713 ◽  
Author(s):  
Jipeng Jin ◽  
Liping Zhang ◽  
Jianlei Jia ◽  
Qian Chen ◽  
Zan Yuan ◽  
...  

The jejunum is the primary organ for digestion and nutrient absorption in mammals. The development of the jejunum in suckling piglets directly affects their growth performance post-weaning. The jejunum microbiome plays an important role in proliferation, metabolism, apoptosis, immune, and homeostasis of the epithelial cells within the organ. The composition and diversity of the gut microbiome is susceptible to the protein composition of the diet. Therefore, the effects of maternal low-protein diets on piglets’ intestinal microbial structure and function have become a hot topic of study. Herein, a maternal low-protein diet was formulated to explore the effects on jejunum microbiome composition and metabolic profiles in Bamei suckling piglets. Using 16S ribosomal RNA (16S rRNA) sequencing in conjunction with bioinformatics analysis, 21 phyla and 297 genera were identified within the gut microflora. The top 10 phyla and 10 genera are within the gut bacteria. Next, KEGG analysis showed that the low-protein diet significantly increased the gut microbial composition, transport and catabolism, immune system, global and overview maps, amino acid metabolism, metabolism of cofactors and vitamins, endocrine system, biosynthesis of other secondary metabolites, signal transduction, environmental adaptation, and cell motility. Taken together, low-protein diets do not appear to affect the reproductive performance of Bamei sows but improved the gut microbiome of the suckling piglets as well as reduced the probability of diarrhea. The data presented here provide new insights on the dietary protein requirements to support the Huzhu Bamei pig industry.


mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Yueqiong Ni ◽  
Jun Li ◽  
Gianni Panagiotou

ABSTRACT As diet is considered the major regulator of the gut ecosystem, the overall objective of this work was to demonstrate that a detailed knowledge of the phytochemical composition of food could add to our understanding of observed changes in functionality and activity of the gut microbiota. We used metatranscriptomic data from a human dietary intervention study to develop a network that consists of >400 compounds present in the administered plant-based diet linked to 609 microbial targets in the gut. Approximately 20% of the targeted bacterial proteins showed significant changes in their gene expression levels, while functional and topology analyses revealed that proteins in metabolic networks with high centrality are the most “vulnerable” targets. This global view and the mechanistic understanding of the associations between microbial gene expression and dietary molecules could be regarded as a promising methodological approach for targeting specific bacterial proteins that impact human health. IMPORTANCE It is a general belief that microbiome-derived drugs and therapies will come to the market in coming years, either in the form of molecules that mimic a beneficial interaction between bacteria and host or molecules that disturb a harmful interaction or proteins that can modify the microbiome or bacterial species to change the balance of “good” and “bad” bacteria in the gut microbiome. However, among the numerous factors, what has proven the most influential for modulating the microbial composition of the gut is diet. In line with this, we demonstrate here that a systematic analysis of the interactions between the small molecules present in our diet and the gut bacterial proteome holds great potential for designing dietary interventions to improve human health.


Author(s):  
Azhar S Sindi ◽  
Donna T Geddes ◽  
Mary E Wlodek ◽  
Beverly S Muhlhausler ◽  
Matthew S Payne ◽  
...  

Abstract Initial colonisation of the infant gut is robustly influenced by regular ingestion of human milk, a substance that contains microbes, microbial metabolites, immune proteins, and oligosaccharides. Numerous factors have been identified as potential determinants of the human milk and infant gut microbiota, including maternal diet; however, there is limited data on the influence of maternal diet during lactation on either of these. Here, we review the processes thought to contribute to human milk and infant gut bacterial colonisation and provide a basis for considering the role of maternal dietary patterns during lactation in shaping infant gut microbial composition and function. Although only one observational study has directly investigated the influence of maternal diet during lactation on the infant gut microbiome, data from animal studies suggests that modulation of the maternal gut microbiota, via diet or probiotics, may influence the mammary or milk microbiota. Additionally, evidence from human studies suggests that the maternal diet during pregnancy may affect the gut microbiota of the breastfed infant. Together, there is a plausible hypothesis that maternal diet during lactation may influence the infant gut microbiota. If substantiated in further studies, this may present a potential window of opportunity for modulating the infant gut microbiome in early life.


Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 4
Author(s):  
Lara Hart ◽  
Charlotte M. Verburgt ◽  
Eytan Wine ◽  
Mary Zachos ◽  
Alisha Poppen ◽  
...  

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician.


2020 ◽  
Author(s):  
E.A. Lopera-Maya ◽  
A. Kurilshikov ◽  
A. van der Graaf ◽  
S. Hu ◽  
S. Andreu-Sánchez ◽  
...  

AbstractHost genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function within the Dutch Microbiome Project, a population cohort of 7,738 individuals from the northern Netherlands. Two robust, study-wide significant (p<1.89×10−10) signals near the LCT and ABO genes were found to affect multiple microbial taxa and pathways, and were replicated in two independent cohorts. The LCT locus associations were modulated by lactose intake, while those at ABO reflected participant secretor status determined by FUT2 genotype. Eighteen other loci showed suggestive evidence (p<5×10−8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.


mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Owen Cronin ◽  
Wiley Barton ◽  
Peter Skuse ◽  
Nicholas C. Penney ◽  
Isabel Garcia-Perez ◽  
...  

ABSTRACT Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to modest but detectable changes in gut microbiota characteristics. For the first time, we show that regular whey protein intake leads to significant alterations to the composition of the gut virome.


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